There is little doubt that the USA faces a growing crisis in tuberculosis control. The rising case rate, after decades of decline, the impact of HIV, and the increasing incidence of multi-drug resistant TB, are all causes for great concern. In view of this, the purpose of the recent issued NIH RFA is to promote research into the development of potential new vaccines active against tuberculosis. The central purpose of this proposal, therefore, is two-fold. Firstly, its intent is to offer a resource for other colleagues in the field who do not themselves have direct access to sophisticated BL-3 level biohazard facilities, to conduct animal studies using established guinea pig and mouse models into the efficacy of new vaccines against tuberculosis, using as a gold standard in both models the capacity of the potential vaccine to protect against aerogenic infection with live virulent M.tuberculosis, including isolates that may be multi-drug resistant. Secondly, we also propose to conduct basic research into the models themselves, particularly with regard to possible ways that the models can be improved, both from scientific and economic aspects. This latter aspect is inter-related, in that new evaluation methods may improve the cost-effectiveness of the existing time consuming and lengthy procedures, while at the same time providing new and valuable immunological information pertaining to the overall efficacy of the new potential vaccine.